Raman spectroscopy is a technique that provides molecular-specific information on biological and chemical samples. However, since Raman signals are intrinsically very weak, various studies have been conducted to enhance the same. Surface-enhanced Raman scattering (SERS) activity can significantly enhance the intensity of the Raman spectra due to absorption energy at a surface. The enhancement factor (EF) used as a measure of the scale of SERS is normally in the range of 104 to 108 and may even reach 1014, which allows detection of single molecules. Most studies with respect to the increase of SERS EF are focused on surface materials and substrate-related fields through modification with nanostructure patterns. Most SERS-active moieties have been prepared by comprehensive and sophisticated methods including lithography or high-temperature processes. While these methods of producing SERS-active substrates involve long, complex steps with a risk of explosion, the use of metal nanoparticles as a SERS substrate provides an easy method of synthesis at low cost and allows size and shape adjustment by reaction conditions, and also agglomerated nanoparticles can significantly improve signaling, thereby providing sensitivity of detection at the level of single molecules (X. M. Lin et al., Anal. Bioanal. Chem., 2009, 394: 1729 to 1745). These nanoparticles exhibit an optical property that absorbs wavelengths used in Raman laser light sources, that is, surface plasmon resonances (SPR) (S. Zeng et al., Chem. Soc. Rev, 2014, 43: 3426 to 3452). In particular, gold, silver, and copper nanoparticles can achieve 103-fold greater enhancement of SERS than other metal substrates (B. Ren et al., Anal. Bioanal. Chem., 2007, 388: 29 to 45). Silver nanoparticles (AgNPs) exhibit superior SERS enhancement compared to gold nanoparticles (AuNPs). However, AgNPs are oxidized in the atmosphere and thus their SERS activity is rapidly reduced, whereas AuNPs form oxide layers and thereby exhibit stable SERS activity.
Meanwhile, paper substrates with economic efficiency (low cost), portability, flexibility, ease of handling, and harmlessness are drawing attention as a novel platform for analytical detection in biomedical and environmental fields (A. W. Martinez et al., Angew. Chemie—Int. Ed., 2007, 46: 1318 to 1320). These user-friendly advantages enable a variety of applications including colorimetric, electrochemical, and biochemical analyses using paper (C. Renault et al., J. Am. Chem. Soc., 2014, 136: 4616 to 4623). These advantages of paper substrates are suitable for point-of-care (POC) applications, but the utilization of paper substrates has a problem in that the restricted detection limit of analytes due to the use of enzymes and redox dyes, and the handling of composite soluble compounds must be overcome.